The Collaborative Ocular Melanoma Study (COMS) randomized trial of pre-enucleation radiation of large choroidal melanoma I: characteristics of patients enrolled and not enrolled COMS report no. 9

doi:10.1016/S0002-9394(98)00038-5

American Journal of Ophthalmology

Volume 125, Issue 6, June 1998, Pages 767-778

https://doi.org/10.1016/S0002-9394(98)00038-5 Get rights and content

Abstract

Purpose: To describe the baseline characteristics and status of patients enrolled in the Collaborative Ocular Melanoma Study (COMS) randomized clinical trial of pre-enucleation radiation of large choroidal melanoma conducted in the United States and Canada, and to compare characteristics of patients enrolled with those of patients with tumors of eligible size who were not enrolled in order to assess the generalizability of findings from the clinical trial.

Methods: For all patients evaluated for the clinical trial at COMS centers from November 1986 through December 15, 1994, selected data were transmitted to the COMS Coordinating Center. For patients who enrolled in the clinical trial, ophthalmic and medical history, examination findings, and visual acuity measurements were recorded prior to enrollment. Standardized A-scan and contact B-scan echographic examinations were performed prior to enrollment, and photoechograms were submitted for central review for consistency with the diagnosis, independent measurement of the apical height of the tumor, and description of tumor configuration and internal reflectivity for each patient enrolled. Until January 1992, wide-angle fundus photographs and fluorescein angiograms taken prior to enrollment also were submitted for central review to confirm consistency with the diagnosis. All data were integrated and analyzed at the COMS Coordinating Center.

Results: Of 6,078 patients with choroidal melanoma evaluated in COMS centers, 1,860 had tumors of eligible size; of these, 1,302 (70%) were eligible for the clinical trial, and 1,003 (77% of eligible patients) enrolled. The two principal reasons for ineligibility were other primary cancer and predominantly ciliary body melanoma. Ineligible patients were older than eligible patients, had larger choroidal melanoma, and had poorer visual acuity at the time of evaluation for the COMS (P < .01, Wilcoxon rank sum tests). Patients eligible for the clinical trial had a mean age of 60 years; 56% were male; almost all (97%) were non-Hispanic whites. Among eligible patients, mean tumor apical height was 9.5 mm and mean longest basal diameter was 17.2 mm. Eligible patients who enrolled in the trial were similar to eligible patients who did not enroll with respect to most factors considered. Those who enrolled had longer tumor basal diameter and better visual acuity in the fellow eye, more often had their primary residence in Canada, and less often had education beyond high school than did eligible patients who did not enroll (P < .05, Wilcoxon rank sum tests and χ² tests, respectively).

Conclusions: The COMS clinical trial of pre-enucleation radiation was designed to yield internally valid treatment comparisons through random treatment assignment at time of enrollment. Findings also have high external validity because a majority (54%) of all patients with tumors of eligible size, and a large majority (77%) of all eligible patients, were enrolled. Furthermore, patient characteristics are similar to those of patients included in other evaluations of this method of treating large choroidal melanoma. Thus, findings from this clinical trial apply to all patients who have large choroidal melanoma and satisfy COMS eligibility criteria.

Section snippets

Patients and methods

Descriptions of some aspects of the COMS design and methods have been published.6, 7, 8, 9, 10 The COMS Manual of Procedures11 and the COMS Forms Book12 are available.

The Data and Safety Monitoring Committee approved the study design and methods on August 27, 1986, prior to initiation of patient evaluation and enrollment. In addition, the institutional review board of each of more than 50 participating institutions reviewed and approved the COMS protocol and the consent forms used at the

Reasons for ineligibility and not enrolling

As of December 15, 1994, the date on which accrual to the COMS trial of pre-enucleation radiation was completed, 6,078 patients with choroidal melanoma of all sizes had been evaluated at COMS clinical centers and reported to the Coordinating Center. Of these patients, 1,860 (31%) had tumors that met the size requirements for this clinical trial. A total of 558 patients (30%) with tumors of appropriate size were ineligible for the randomized trial of pre-enucleation radiation. One hundred

Discussion

At the time the COMS was designed, a decision was made to collect descriptive information about all patients with choroidal melanoma who were evaluated at participating clinical centers.7, 23 Although the amount of information collected has been reduced during the course of the COMS, this policy has continued to the present time. The primary purpose for collecting this information was to project the time period required to accrue the target sample sizes for COMS clinical trials and to estimate

Acknowledgements

The COMS investigators are grateful to the ophthalmologic community for supporting COMS clinical trials of radiotherapy by referring patients with choroidal melanoma to participating clinical centers.

References (27)

B.R. Straatsma et al.
Enucleation versus plaque irradiation for choroidal melanoma
Ophthalmology
(1988)
F.L. Ferris et al.
New visual acuity charts for clinical research
Am J Ophthalmol
(1982)
A.P. Schachat et al.
Nonocular cancers in patients with choroidal melanoma [letter]
Ophthalmology
(1990)
K.M. Egan et al.
Epidemiologic aspects of uveal melanoma
Surv Ophthalmol
(1988)
M. Diener-West et al.
Sociodemographic characteristics associated with patient enrollment in the Collaborative Ocular Melanoma Study [abstract]
Controlled Clin Trials
(1991)
D.H. Char et al.
Failure of preenucleation radiation to decrease uveal melanoma mortality
Am J Ophthalmol
(1988)
G.P.M. Luyten et al.
No demonstrated effect of pre-enucleation irradiation on survival of patients with uveal melanoma
Am J Ophthalmol
(1995)
J. Scotto et al.
Melanomas of the eye and other noncutaneous sitesepidemiologic aspects
J Natl Cancer Inst
(1976)
W.A. Manschot et al.
Choroidal melanoma: enucleation or observation? A new approach
Arch Ophthalmol
(1980)
P. Lommatzsch et al.
The effect of orbital irradiation on the survival rate of patients with choroidal melanoma
Ophthalmologica
(1976)

D.H. Char et al.

The potential for adjuvant radiotherapy in choroidal melanoma

Arch Ophthalmol

(1982)

D.H. Char et al.

Pre-enucleation irradiation of uveal melanoma

Br J Ophthalmol

(1985)

Design and methods of a clinical trial for a rare condition: the Collaborative Ocular Melanoma Study. COMS report no. 3

Controlled Clin Trials

(1993)

Cited by (94)

Brachytherapy of Choroidal Melanomas Less Than 10 mm in Largest Basal Diameter: Comparison of 10-mm and 15-mm Ruthenium Plaques
2021, Ophthalmology
Citation Excerpt :
Causes of death were verified from death certificates and patient charts. We assessed the visual outcome after the conventions of the Collaborative Ocular Melanoma Study.12 Measurements worse than 20/1600, such as counting fingers or hand movements, were set to 20/1600.
To compare tumor control, vision, and complications between patients with a choroidal melanoma of <10 mm in largest basal diameter (LBD) irradiated with 10-mm or 15-mm ruthenium plaques.
Retrospective, comparative case series.
One hundred sixty-four consecutive patients with a choroidal melanoma of <10 mm in LBD, 76 and 88 treated with the 10-mm and 15-mm plaque, respectively, from 1998–2014 in a national ocular oncology service.
Diagnosis was based on growth or high-risk characteristics. The apical dose was 100 to 120 Gy aiming to deliver ≥250 Gy to the sclera. Plaque positioning was modeled retrospectively. An increase of ≥0.3 mm in thickness and ≥0.5 mm in LBD indicated local recurrence. Outcomes were compared with cumulative incidence analysis and Cox regression. Median follow-up time for patients still alive was 8.4 years.
Recurrence rate, low vision, blindness, radiation maculopathy, and optic neuropathy.
Melanomas treated with the 10-mm plaque were smaller (median thickness, 1.9 mm vs. 2.6 mm; LBD, 7.1 mm vs. 8.6 mm) and located closer to foveola (median, 2.0 mm vs. 2.8 mm) than those treated with the 15-mm plaque (P < 0.001). The 2 plaques provided a safety margin in 43% versus 40% eyes, provided no safety margin to guard foveola in 17% versus 33%, and did not entirely cover tumor mainly close to the disc in 32% versus 18% of eyes, respectively (P = 0.052). The incidence of a local recurrence was comparable (13% vs. 15% at 10 years; P = 0.31) and associated with plaque positioning (hazard ratio [HR], 2.81 for no safety margin; P = 0.041). At 5 years, the incidence of low vision was 14% versus 24%, and that of blindness was 3% versus 6%. Distance to the foveola was associated with loss of both levels of vision (HR, 0.65 per 1 mm vs. 0.68 per 1 mm; P ≤ 0.001 vs. P = 0.004). The incidence of radiation maculopathy was comparable (19% vs. 18% at 5 years), whereas that of optic neuropathy tended to be higher with the 15-mm plaque (2% vs. 9%; P = 0.054).
The 10-mm ruthenium plaque contributes to better visual preservation, particularly with tumors close to fovea, without increase in local recurrence rate, and may therefore be preferable to the 15-mm plaque.
Ocular Tumors
2019, Abeloff’s Clinical Oncology
Ocular tumors are rare enough that many general ophthalmologists will see only one to a handful during a career. Ocular tumors encompass a wide spectrum of disorders and can be divided into intraocular, conjunctival, eyelid and orbital tumors. The basis of ocular tumor management historically has been biased towards excisional therapy or enucleation, resulting in significant morbidity and loss of vision. More recently treatments have emerged which salvage the globe, do not decrease the survival rate. As we continue to learn more about the etiology, genetics, the molecular pathways of these tumors, there is hope that new therapeutic approaches will evolve. We review the pathology, epidemiology, clinical features, treatment options and future management directions of the most common intraocular tumors.
Factors affecting patient participation in orthopaedic trials comparing surgery to non-surgical interventions
2016, Contemporary Clinical Trials Communications
Randomized controlled trials (RCTs) are considered the most robust research design to determine the effectiveness of interventions. RCTs comparing surgery to non-surgical alternatives are particularly difficult to perform, partly due to difficulties with recruitment. Low recruitment rates can limit the internal and external validity of a trial thus understanding their causes may be important for avoiding protracted recruitment periods. This study aimed to report patient factors that influenced participation in a trial comparing surgery to a non-surgical treatment approach.
This study was a cross-sectional study nested within CROSSBAT (Combined Randomized and Observational Study of Surgery For Type B Ankle Fracture Treatment). Eligible participants willing to be randomized were randomized while those who declined randomization were offered participation in an observational cohort. Participants from both groups (randomized and observational) were asked to indicate their level of agreement on a 100 mm line with statements concerning reasons for acceptance or rejection of randomization. A subset were asked to state the primary reason for agreeing to participate or not in the trial.
The nested study included 312 participants; 113 who accepted and 199 who declined randomization. Participants unwilling to be randomized (those in the observational arm of the study) predominantly received a non-surgical intervention. They were significantly more worried about receiving treatment by chance (55 mm vs. 33 mm; p < 0.0001) and had a significantly higher preference for one particular treatment (less equipoise) (82 mm vs 43 mm; p < 0.0001) compared to participants willing to be randomized. Influence from clinicians and risk avoidance were primary influences of participation. Participants’ responses regarding protocol burden, study follow-up requirements and altruism did not significantly differ between groups.
Patient non-participation in an RCT comparing surgery to no surgery is related to concern about receiving a treatment through chance and the presence of a strong preference for a particular treatment, particularly a non-surgical one. To avoid protracted recruitment periods, investigators can increase the number of study sites and ensure personnel involved have equipoise and are trained to provide a balanced view of both treatment arms.
The pediatric choroidal and ciliary body melanoma study: A survey by the European Ophthalmic Oncology Group
2016, Ophthalmology
To collect comprehensive data on choroidal and ciliary body melanoma (CCBM) in children and to validate hypotheses regarding pediatric CCBM: children younger than 18 years, males, and those without ciliary body involvement (CBI) have more favorable survival prognosis than young adults 18 to 24 years of age, females, and those with CBI.
Retrospective, multicenter observational study.
Two hundred ninety-nine patients from 24 ocular oncology centers, of whom 114 were children (median age, 15.1 years; range, 2.7–17.9 years) and 185 were young adults.
Data were entered through a secure website and were reviewed centrally. Survival was analyzed using Kaplan-Meier analysis and Cox proportional hazards regression.
Proportion of females, tumor-node-metastasis (TNM) stage, cell type, and melanoma-related mortality.
Cumulative frequency of having CCBM diagnosed increased steadily by 0.8% per year of age between 5 and 10 years of age and, after a 6-year transition period, by 8.8% per year from age 17 years onward. Of children and young adults, 57% and 63% were female, respectively, which exceeded the expected 51% among young adults. Cell type, known for 35% of tumors, and TNM stage (I in 22% and 21%, II in 49% and 52%, III in 30% and 28%, respectively) were comparable for children and young adults. Melanoma-related survival was 97% and 90% at 5 years and 92% and 80% at 10 years for children compared with young adults, respectively (P = 0.013). Males tended to have a more favorable survival than females among children (100% vs. 85% at 10 years; P = 0.058). Increasing TNM stage was associated with poorer survival (stages I, II, and III: 100% vs. 86% vs. 76%, respectively; P = 0.0011). By multivariate analysis, being a young adult (adjusted hazard rate [HR], 2.57), a higher TNM stage (HR, 2.88 and 8.38 for stages II and III, respectively), and female gender (HR, 2.38) independently predicted less favorable survival. Ciliary body involvement and cell type were not associated with survival.
This study confirms that children with CCBM have a more favorable survival than young adults 18 to 25 years of age, adjusting for TNM stage and gender. The association between gender and survival varies between age groups.
Learning from the experience of collaborative research on ocular melanoma to improve the diagnosis and treatment level of uveal melanoma in China
2023, Chinese Journal of Ocular Fundus Diseases
Long-Term Outcomes in Uveal Melanoma After Ruthenium-106 Brachytherapy
2022, Frontiers in Oncology

View all citing articles on Scopus

^☆: The COMS has received support from the National Eye Institute and the National Cancer Institute through cooperative agreements EY06253, EY06257, EY06258, EY06259, EY06260, EY06264, EY06265, EY06266, EY06268, EY06269, EY06270, EY06274, EY06275, EY06276, EY06279, EY06280, EY06282, EY06283, EY06284, EY06287, EY06288, EY06289, EY06291, EY06839, EY06843, EY06844, EY06848, EY06858, and EY06899 with the National Institutes of Health, Bethesda, Maryland.

^∗: A complete listing of the COMS Group as of August 31, 1997, begins on page 757.

View full text

Original ArticlesThe Collaborative Ocular Melanoma Study (COMS) randomized trial of pre-enucleation radiation of large choroidal melanoma I: characteristics of patients enrolled and not enrolled COMS report no. 9☆

Abstract

Section snippets

Patients and methods

Reasons for ineligibility and not enrolling

Discussion

Acknowledgements

Ophthalmology

Am J Ophthalmol

Ophthalmology

Surv Ophthalmol

Controlled Clin Trials

Am J Ophthalmol

Am J Ophthalmol

Melanomas of the eye and other noncutaneous sitesepidemiologic aspects

J Natl Cancer Inst

Choroidal melanoma: enucleation or observation? A new approach

Arch Ophthalmol

The effect of orbital irradiation on the survival rate of patients with choroidal melanoma

Ophthalmologica

The potential for adjuvant radiotherapy in choroidal melanoma

Arch Ophthalmol

Pre-enucleation irradiation of uveal melanoma

Br J Ophthalmol

Design and methods of a clinical trial for a rare condition: the Collaborative Ocular Melanoma Study. COMS report no. 3

Controlled Clin Trials

Original Articles
The Collaborative Ocular Melanoma Study (COMS) randomized trial of pre-enucleation radiation of large choroidal melanoma I: characteristics of patients enrolled and not enrolled COMS report no. 9☆